Study of Genetic and Epigenetic Influences on Adolescents Following Bariatric Surgery

Objective

To create biology models of the cardiometabolic changes induced by bariatric surgery.This model will integrate changes across several human tissues involved in metabolism, including skeletal muscle, liver and adipose. They plan to study genetic and epigenetic influences on molecular and clinical changes in adolescents following bariatric surgery.

Study Design

Eight non-diabetic and 8 diabetic African American women will be recruited from patients in the ECU Department of Surgery Bariatric Surgery Clinic. They will be informed about the procedures and risks and then consented for the study. They will have a blood sample, a skeletal muscle biopsy and an adipose tissue biopsy taken 2-4 weeks before their gastric bypass surgery. At the time of the gastric bypass operation the surgeon will remove a small liver biopsy and a small biopsy of intra-abdominal adipose tissue. One year after surgery the patients will have a second blood sample, muscle biopsy and subcutaneous adipose tissue biopsy. On a separate occasion, at one year post-surgery, the patient will have an ultrasonic guided liver biopsy. The de-identified blood samples and all tissue biopsies will be sent to the investigators at Children’s National Medical Center for analysis. Genomic DNA will be isolated from baseline whole blood. Genotypes associated with obesity/Type 2 diabetes will be tested. Serum and plasma from each time point will be screened for metabolites (i.e. fatty acids, amino acids, small hormones by mass spectrometer). All tissues will be processed in parallel for DNA (epigenetic modifications by methylation array), mRNA and miRNA (transcriptomics by microarray), and protein. Integration of these data in a longitudinal design will test for differences between diabetics and non-diabetics in their ability to respond to surgery.

Inclusion Criteria:

1)African American Females

2)25-60 years of age

3)BMI of 35 to 65

4)Willing to comply with study requirements and long term follow-up

5)Capable of understanding the requirements and consequences of surgery and the study

6)Is scheduled to have laparoscopic gastric bypass performed

7)Has a negative pregnancy test

Exclusion Criteria:

1)Repeat gastric bypass procedure

2)Patients taking TZD’s (thiazolidinediones).

Compensation

Volunteers will be paid $100 for undergoing muscle and adipose tissue biopsies as well as a fasting blood draw on two occasions, once before surgery and again 1 year after surgery. In addition, patients will be paid $200 to have an ultrasound guided liver biopsy one year after surgery. This is a potential total compensation of $400. This stipend is intended to compensate subjects for their time devoted to the study and any physical discomfort.